Microsphere type sustained-release drug preparations incorporating a biodegradable polymer are disclosed in, for example, Japanese Patent Unexamined Publication Nos. 118512/1982, 150609/1982, 100516/1985 (EP-A145240), 201816/1987 (EP-A190833), 233926/1988, 42420/1989, 032302/1991, 321622/1922 (EP-A442671), 70363/1993, 112468/1993, 194200/1993 (EP-A535937), 145046/1994 (EP-A582459) and 192068/1994 (EP-A586238). Japanese Patent Unexamined Publication Nos. 100516/1985 and 201816/1987, in particular, disclose a method of preparing sustained-release microspheres of a water-soluble physiologically active substance with high entrapment ratio and high dispersibility by the in-water drying method.
With regard to microsphere type sustained-release drug preparations incorporating a biodegradable polymer, it is necessary to prepare fine particles of uniform microsphere particle form, to ensure satisfactory dispersibility and needle passability during administration, and to prevent aggregation and particle binding from market delivery to use. Also, in the preparation method involving the use of an organic solvent, the residual solvent in the finished preparation is problematic from the viewpoint of preparation stability and safety to the human body, necessitating perfect solvent removal during the production process.